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Biomedical subjects

D Nielsen

Publications and source records attributed to D Nielsen.

At least 19 recordsLinked to original sources
PubMed2004

Monitoring different stages of breast cancer using tumour markers CA 15-3, CEA and TPA.

The ability of the tumour markers Cancer Antigen 15-3 (CA 15-3), Carcinoembryonic Antigen (CEA), and Tissue Polypeptide Antigen (TPA) to signal progression in breast cancer patients was investigated in this study. Marker interpretation considered the analytical variation, intra-individual biological variation, and the rate of increase. Patient cohorts were as follows: (A) 90 stage II breast cancer patients who were monitored postoperatively, (B) 204 recurrent breast cancer patients who were monitored during first-line chemotherapy, and (C) 112 patients who were monitored during the time period after first-line chemotherapy. The sensitivity for progression was 44% (cohort A), 69% (cohort B), and 68% (cohort C) without any false progression signals. Marker lead-times exceeded 3 months in 20% (cohort A) and 27% (cohort C) of patients. Marker lead-times were 1-6 months among 33% of the patients receiving first-line chemotherapy (cohort B). Trials are necessary to determine whether tumour marker-guided therapy has any prognostic impact. The data suggest that tumour marker information may be used to stop ineffective treatments and reduce unnecessary adverse effects.

Antineoplastic Agents↗
PubMed2003

The relative glucose uptake abilities of non-Saccharomyces yeasts play a role in their coexistence with Saccharomyces cerevisiae in mixed cultures.

The growth and glucose uptake of single cultures of the wine-related yeasts Kluyveromyces thermotolerans, Torulaspora delbrueckii, and Saccharomyces cerevisiae were investigated. The yeasts had different specific glucose uptake rates (qs) that depended on the residual glucose concentration and the oxygen availability. In mixed cultures, the qs values of the yeasts were not subject to any interaction effects over a wide range of glucose concentrations. Our results strongly indicate that the relative glucose uptake abilities of both non-Saccharomyces yeasts, i.e. the qs(non-Saccharomyces)/qs(S. cerevisiae) ratios, regulated their abilities to compete for space in mixed cultures with S. cerevisiae, which, in turn, regulated their early deaths. This hypothesis enabled us to explain why K. thermotolerans was less able than T. delbrueckii to coexist with S. cerevisiae in mixed cultures. Furthermore, it enabled us to explain why oxygen increased the abilities of K. thermotolerans and T. delbrueckii to coexist with S. cerevisiae in the mixed cultures.

Colony Count, Microbial↗
PubMed2003

FISH analysis for chromosomes 13, 16, 18, 21, 22, X and Y in all blastomeres of IVF pre-embryos from 144 randomly selected donated human oocytes and impact on pre-embryo morphology.

BACKGROUND: The data are compiled from two multicentre, prospectively randomized studies on the effect of follicular fluid meiosis-activating sterol (FF-MAS) on human oocytes. The donated oocytes were exposed either to test doses of FF-MAS or to control solutions. The data from the control groups are presented with chromosomal status of the embryos correlated to embryo morphology. METHODS: The study includes 144 randomly selected donated human oocytes. The nucleus from each blastomere was fixed separately and fluorescence in-situ hybridization (FISH) using seven probes (13, 16, 18, 21, 22, X and Y) was performed. RESULTS: Analysis of 103 pre-embryos containing 479 blastomeres resulted in 424 blastomeres with clear FISH signals. Of these blastomeres, 55% were normal diploid and 45% were abnormal. At a pre-embryonic level, 53% were classified as normal containing >or=50% normal blastomeres while 31% of the pre-embryos were classified as uniformly normal. Abnormality rate was significantly increased in the pre-embryos with unevenly sized blastomeres and with increasing degree of fragmentation at 68 h after fertilization. Applying criteria for good embryo quality significantly increased the rate of chromosomally normal pre-embryos from 53 to 75%. CONCLUSIONS: The data demonstrate the high degree of genetic heterogeneity in a randomly selected pool of donated pre-embryos from an IVF programme. Further, we found that uniformity of blastomere size, degree of fragmentation and cleavage kinetics reflect the cytogenetic status of the pre-embryo and are therefore important in the selection of pre-embryos.

Blastomeres↗
PubMed2002

Occupational accidents aboard merchant ships.

OBJECTIVES: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational accidents as well as dangerous working situations where possible preventive measures may be initiated. METHODS: The study is a historical follow up on occupational accidents among crew aboard Danish merchant ships in the period 1993-7. Data were extracted from the Danish Maritime Authority and insurance data. Exact data on time at risk were available. RESULTS: A total of 1993 accidents were identified during a total of 31 140 years at sea. Among these, 209 accidents resulted in permanent disability of 5% or more, and 27 were fatal. The mean risk of having an occupational accident was 6.4/100 years at sea and the risk of an accident causing a permanent disability of 5% or more was 0.67/100 years aboard. Relative risks for notified accidents and accidents causing permanent disability of 5% or more were calculated in a multivariate analysis including ship type, occupation, age, time on board, change of ship since last employment period, and nationality. Foreigners had a considerably lower recorded rate of accidents than Danish citizens. Age was a major risk factor for accidents causing permanent disability. Change of ship and the first period aboard a particular ship were identified as risk factors. Walking from one place to another aboard the ship caused serious accidents. The most serious accidents happened on deck. CONCLUSIONS: It was possible to clearly identify work situations and specific risk factors for accidents aboard merchant ships. Most accidents happened while performing daily routine duties. Preventive measures should focus on workplace instructions for all important functions aboard and also on the prevention of accidents caused by walking around aboard the ship.

Accidents, Occupational↗
PubMed2001

Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation.

PURPOSE: To characterize irradiated murine tumor cells with respect to drug resistance, drug kinetics, and ATPase activity, and to evaluate the possible role of P-glycoprotein (PGP) and murine multidrug resistance associated protein (Mrp1) in the drug-resistant phenotype of these cells. METHODS AND MATERIALS: Sensitive Ehrlich ascites tumor cells (EHR2) were in vitro exposed to fractionated irradiation (60 Gy). Western blot analysis was performed for determination of PGP and Mrp1, reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of mdr1a + b mRNA, and semiquantitative RT-PCR for Mrp1 mRNA. The clonogenic assay was applied to investigate sensitivity, whereas the steady-state drug accumulation of daunorubicin (DNR), 3H-vincristine (VCR), and 3H-etoposide (VP16) was measured by spectrofluorometry and scintillation counting, respectively. For determining of ATPase activity, the release of inorganic phosphate from ATP was quantified using a colorimetric method. RESULTS: Compared with EHR2, the irradiated cell line EHR2/irr showed increased expression of PGP (threefold), Mrp1 (eightfold), and Mrp1 mRNA (sixfold), and a slight reduction of mdr1b mRNA, whereas mdr1a was present in EHR2 but could not be detected in EHR2/irr. EHR2/irr developed sixfold resistance to VP16, twofold resistance to vincristine, but remained sensitive to DNR. Addition of the PGP inhibitor, verapamil (VER) or depletion of glutathione by buthionine sulfoximine (BSO) partly reversed the resistance in EHR2/irr. In EHR2/irr, the steady-state accumulation of 3H-VCR and 3H-VP16 was significantly decreased as compared with EHR2, whereas the accumulation of DNR was unchanged. The ATPase activity of plasma membrane vesicles prepared from EHR2/irr cells was similar to that of wild-type EHR2 cells. The ATPase activity was neither stimulated by vinblastine nor VER. CONCLUSION: Irradiation induced a multidrug-resistant phenotype in sensitive tumor cells. This phenotype was characterized by increased expression of Mrp1 mRNA, Mrp1, and PGP but decreased expression of mdr1a + b mRNA. The influence of irradiation on PGP and Mrp1 expression seemed to be different.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Evolution of the simulated data problem.

The simulated data problem was designed via an interactive process by the Simulation Problem Organizing Committee and the selected data simulators. Based on discussions at the previous Genetic Analysis Workshop, many of the features of previous simulation problems, such as a complex disease, genome scan, and replication, were retained and in addition, a population genetics model was used to generate the simulated genes. We describe the process that was used to structure the problem and summarize the discussions about many of the scientific issues that were considered.

Chromosome Mapping↗
PubMed2001

GAW12: simulated genome scan, sequence, and family data for a common disease.

The Genetic Analysis Workshop (GAW) 12 simulated data involves a common disease defined by imposing a threshold on a quantitative liability distribution. Associated with the disease are five quantitative risk factors, a quantitative environmental exposure, and a dichotomous environmental variable. Age at disease onset and household membership were also simulated. Genotype data, including 2,855 microsatellites on 22 autosomes, were simulated for 1,497 individuals in 23 families. Phenotype data and sequence data for seven candidate genes were provided for 1,000 of these individuals who were "living" and available for study. Data were simulated for 50 replicate samples in each of two populations, a general population and a population isolate formed from a small group of founders.

Adolescent↗
PubMed2001

Prognostic factors and long-term survival in 585 patients with metastatic breast cancer treated with epirubicin-based chemotherapy.

BACKGROUND: Analysis of prognostic factors in patients with metastatic breast cancer treated with epirubicin-based chemotherapy. PATIENTS AND METHODS: Data from 469 patients treated with epirubicin-based chemotherapy for metastatic breast cancer were used. Prognostic factors were identified (Cox multivariate analysis). A prognostic index was compiled and risk groups were established accordingly. The applicability of the index was investigated in a series of 116 patients. RESULTS: The prognostic factors identified were: liver, pleural, soft tissue, lung and bone metastases, performance status > 2, advancing age, abnormal elevation of serum lactate dehydrogenase and negative/unknown oestrogen receptor status. Four risk groups were established: good, intermediate I, intermediate II and poor. The median and five-year survivals in percentage were: good: 34 months (26%); intermediate I: 19 months (6%), intermediate II: 12 months (0%); poor: 7 months (1%). The corresponding values in the applicability group were: 32 months (23%); 28 months (22%); 18 months (5%); and 6 months (0%). CONCLUSIONS: It is more the number and impact on the organs involved, that predict the patients' survival. The construction of a prognostic index could be helpful in assessing the outlook for patients, especially the quite dramatic difference in long-term survival between the good and poor risk patients.

Adult↗
PubMed2001

Dwarf8 polymorphisms associate with variation in flowering time.

Historically, association tests have been used extensively in medical genetics, but have had virtually no application in plant genetics. One obstacle to their application is the structured populations often found in crop plants, which may lead to nonfunctional, spurious associations. In this study, statistical methods to account for population structure were extended for use with quantitative variation and applied to our evaluation of maize flowering time. Mutagenesis and quantitative trait locus (QTL) studies suggested that the maize gene Dwarf8 might affect the quantitative variation of maize flowering time and plant height. The wheat orthologs of this gene contributed to the increased yields seen in the 'Green Revolution' varieties. We used association approaches to evaluate Dwarf8 sequence polymorphisms from 92 maize inbred lines. Population structure was estimated using a Bayesian analysis of 141 simple sequence repeat (SSR) loci. Our results indicate that a suite of polymorphisms associate with differences in flowering time, which include a deletion that may alter a key domain in the coding region. The distribution of nonsynonymous polymorphisms suggests that Dwarf8 has been a target of selection.

Genes, Plant↗
PubMed2001

Seafarers' accidents: does age, rank or experience matter?

Studies on the work-related accidents among seafarers conducted in various countries during the 1980s and 1990s are reviewed, with particular reference to the age, rank and job experience of the victims. The lack of reliable and comparable statistical data on these accidents is a matter of concern. The author suggests that a better subdivision of accident causes and types would be necessary to monitor trends in rates, and to improve the legislation and work practices which could lead to reduction of these accident and fatality rates.

Accidents, Occupational↗
PubMed2000

Characterisation of non-P-glycoprotein multidrug-resistant Ehrlich ascites tumour cells selected for resistance to mitoxantrone.

An Ehrlich ascites tumour cell line (EHR2) was selected in vivo for resistance to mitoxantrone (MITOX). The resistant cell line (EHR2/MITOX) was 6123-, 33-, and 30-fold-resistant to mitoxantrone, daunorubicin, and etoposide, respectively, but retained sensitivity to vincristine. The resistant cells showed moderate sensitisation to mitoxantrone on treatment with verapamil or cyclosporin A. Compared with EHR2, the multidrug resistance-associated protein mRNA was increased 13-fold in EHR2/MITOX. Western blot analysis showed an unchanged, weak expression of P-glycoprotein. Topoisomerase IIalpha was reduced to one-third in EHR2/MITOX relative to EHR2 cells, whereas topoisomerase IIbeta was present in EHR2 but could not be detected in EHR2/MITOX. In the resistant subline, net accumulation of MITOX (120 min) and daunorubicin (60 min) was reduced by 43% and 27%, respectively, as compared with EHR2. The efflux of daunorubicin from preloaded EHR2/MITOX cells was significantly increased. EHR2/MITOX microsomes had a significant basal unstimulated ATPase activity. The apparent K(i) value for vanadate inhibition of the ATPase activity in EHR2/MITOX microsomes was not significantly different from the K(i) value for P-glycoprotein-positive cells. However, whereas verapamil (50 microM) inhibited the ATPase activity of EHR2/MITOX microsomes, it stimulated the ATPase activity of microsomes derived from P-glycoprotein-positive cells. In conclusion, the resistance in EHR2/MITOX was multifactorial and appeared to be associated with: 1) a quantitative reduction in topoisomerase IIalpha and beta protein; 2) reduced drug accumulation, probably as a result of increased expression of a novel transport protein with ATPase activity; and 3) increased expression of MRP mRNA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide.

An Ehrlich ascites tumour cell line (EHR2) was selected for resistance to etoposide (VP16) by in vivo exposure to this agent. The resulting cell line (EHR2/VP16) was 114.3-, 5.7-, and 4.0-fold resistant to VP16, daunorubicin, and vincristine, respectively. The amount of salt-extractable immunoreactive topoisomerase IIalpha and beta in EHR2/VP16 was reduced by 30-40% relative to that in EHR2. The multidrug resistance-associated protein (MRP) mRNA was increased 20-fold in EHR2/VP16 as compared with EHR2, whereas the expression of P-glycoprotein was unchanged. In EHR2/VP16, the steady-state accumulation of [(3)H]VP16 and daunorubicin was reduced by 64% and 17%, respectively, as compared with EHR2. Deprivation of energy by addition of sodium azide increased the accumulation of both drugs to the level of sensitive cells. When glycolysis was restored by the addition of glucose to EHR2/VP16 cells loaded with drug in the presence of sodium azide, extrusion of [(3)H]VP16 and daunorubicin was induced. Addition of verapamil (25 microM) decreased the efflux of daunorubicin to the level of sensitive cells, but had only a moderate effect on the efflux of [(3)H]VP16. The resistant cells showed moderate sensitisation to VP16 on treatment with verapamil, whereas cyclosporin A had no effect. Compared with that of sensitive cells, the ATPase activity of plasma membrane vesicles prepared from EHR2/VP16 cells was very low. Vanadate inhibited the ATPase activity of EHR2/VP16 microsomes with a K(i) value of 30 microM. ATPase activity was slightly stimulated by daunorubicin, whereas vinblastine, verapamil, and cyclosporin A had no effect. In conclusion, development of resistance to VP16 in EHR2 is accompanied by a significant reduction in topoisomerase II (alpha and beta) and by increased expression of MRP mRNA (20-fold). MRP displays several points of resemblance to P-glycoprotein in its mode of action: 1) like P-glycoprotein, MRP causes resistance to a range of hydrophobic drugs; 2) MRP decreases drug accumulation in the cells and this decrease is abolished by omission of energy; and 3) MRP increases efflux of drug from cells. However, compared with that of P-glycoprotein-positive cells, the ATPase activity of MRP-positive cells is found to be low and not able to be stimulated by verapamil.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Rehabilitation of patients with chronic obstructive lung disease. Are two exercise sessions per week sufficient?].

Several studies of patients with chronic obstructive pulmonary disease (COPD) have shown that pulmonary rehabilitation three to seven times a week improves exercise performance and well being. This study investigates feasibility, effect and economic aspects of a programme consisting of two sessions a week. Twenty-four patients were randomized to rehabilitation and twenty-one to placebo. In an outpatient setting patients were assigned to an eight-week programme of exercise plus education twice a week (Exercise group) or conventional community cares (Placebo group). Seven patients did not complete the rehabilitation. The characteristics of the thirty-eight COPD patients at baseline (mean +/- SD): forced expiratory volume in one second (FEV-1) 1.1 +/- 0.4 L, six-minute walk distance (6MWD) 413 +/- 75 m. Rehabilitation resulted in an insignificant improvement in well being and the 6MWD (29 m ¿95% confidence interval: -8-66 m¿. Rehabilitation session twice a week for eight weeks had no effect in patients with moderate COPD.

Adult↗
PubMed2000

Effect of topotecan on serum CA-125 in patients with advanced epithelial ovarian cancer.

The effect of topotecan on CA-125 serum levels was evaluated in 30 patients with advanced epithelial ovarian cancer. All patients had progressive disease and were relapsing during (11 patients) or after (19 patients) chemotherapy containing paclitaxel and platinum. Topotecan (1.0 mg/m(2)/day) was administered intravenously on Days 1-5 every 3 weeks. The patients had received a median of 2 (1-5) prior regimens. Four patients had increased CA-125 only, and 26 had both measurable disease and increased CA-125. Two patients (7%) achieved a clinical partial response with durations of 5 and 10+ months, respectively. Eighteen other patients (60%) exhibited no clinical change with a median duration of 5+ months (range: 2-11+ months). Among these patients 9 (30%) had a biochemical response. The rate of change in CA-125 (s, slope of the exponential regression curve) during treatment with topotecan was compared with s over a period before treatment. A decrease in s was observed in 20 patients (74%). Comparing the mean values of s before and during topotecan, a significant (P = 0.005) decrease was seen in the CA-125 serum levels. The mean doubling times before and during treatment were 59 and 1421 days, respectively. Toxicity was mainly hematologic. Neutropenia grades III and IV were seen in 16 and 10 patients, respectively. No patients died due to side effects. Generally the side effects were mild to moderate. In conclusion, at the given dose intensity topotecan shows activity in advanced paclitaxel- and platinum-resistant ovarian cancer based on CA-125 measurements.

Adult↗
PubMed2000

Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study.

PURPOSE: To compare the efficacy and toxicity of epirubicin to that of the combination of epirubicin and cisplatin in patients with advanced breast cancer. PATIENTS AND METHODS: A total of 155 patients were randomized to receive either epirubicin (70 mg/m2) days 1 and 8 every 4 weeks or epirubicin (60 mg/m2) days 1 and 8 plus cisplatin (100 mg/m2) day 1 every 4 weeks. Epirubicin was continued until disease progression or to a cumulative dose of 1000 mg/m2. Cisplatin was discontinued after six cycles. In 45 premenopausal women an oophorectomy was performed. None of the evaluable patients had received chemotherapy for metastatic disease. RESULTS: Among evaluable patients (74 in the epirubicin group and 65 in the epirubicin plus cisplatin group) there were 19% vs 29% complete responses, and 42% vs 37% partial responses, with no significant difference. In the epirubicin plus cisplatin group the response rate was significantly higher in previously untreated patients as compared with patients who had received adjuvant chemotherapy (74% vs 55%, P = 0.002). Median times to disease progression were 8.4 months in the epirubicin group and 15.3 months in the epirubicin plus cisplatin group (P = 0.045). Median survival times were 15.1 and 21.5 months, respectively (P = 0.41). In the epirubicin plus cisplatin group leukopenia and thrombocytopenia were significantly more frequent, 29% of the patients developed mild to moderate peripheral neurotoxicity, 34% reported tinnitus and hearing changes, 6 patients developed nephrotoxicity (one died due to nephrotic syndrome), and 3 patients developed leukaemia (two died of this cause). Congestive heart failure occurred in six patients in the epirubicin group and three patients in the epirubicin plus cisplatin group. CONCLUSION: Cisplatin plus epirubicin is an active, although highly toxic regimen when used as first-line therapy in advanced breast cancer. The time to disease progression was significantly longer in the cisplatin plus epirubicin group (increased by 82%). Due to toxicity, the combination regimen cannot be recommended. However, the study indicated a very high activity of cisplatin in advanced breast cancer. Studies of first-line therapy in advanced breast cancer including cisplatin or other platin derivatives in combination with, for example, the taxanes are suggested.

Adult↗
PubMed2000

Second-line treatment of small-cell lung cancer with the camptothecin-derivative GI147211: a study of the EORTC Early Clinical Studies Group (ECSG).

BACKGROUND: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was brought into clinical development because of its higher water solubility and greater potency as compared to topotecan (TPT). The antitumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no response to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle). PATIENTS AND METHODS: Sixty-seven patients were entered in the study and sixty-two were evaluable for response, twenty-eight in the refractory and thirty-four in the chemosensitive group. All patients had received 1 line of chemotherapy; radiation had also been given in 29 cases, 6 in the refractory and 23 in the chemosensitive group. GI147211 was administered at 1.2 mg/m2/day as 30-min infusion for five consecutive days every three weeks. RESULTS: The overall response rate was 16.6% (11 of 66 patients; 95% confidence interval (95% CI): 8.5%-27.5%), 10.3% (3 of 29 patients; 95% CI: 2.2%-27%) in the refractory and 21.1% (8 of 37 patients; 95% CI: 9.5%-37%) in the chemosensitive group. Only partial responses (PR) were observed with a median duration of PR of 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitive group). Hematological toxicity consisted mainly of neutropenia (grades 3-4 in 25% of cycles) and thrombocytopenia (grades 3-4 in 23% of cycles); non-hematological toxicity was mild to moderate and consisted of nausea (22% of cycles), vomiting (11%), malaise (34%). CONCLUSIONS: At the dose and schedule tested GI147211 is an active new agent for second-line treatment of SCLC; the antitumor activity and toxicity profile are comparable to those observed with TPT which remains the leading CPT analogue for salvage treatment. Interest has been renewed in the clinical development of GI147211 by preclinical data with the liposomal formulation showing an increased therapeutic index.

Adult↗